METABOLISM OF AUTOCRINE PEPTIDES--SMALL CELL LUNG CANCER

小细胞肺癌(即小燕麦细胞癌)占 约占所有可识别的人类肺癌的25%。这 恶性肿瘤的生长速度很快，表现为 转移和快速生长的倾向。仅在亚利桑那州， 每年有2400例新诊断的肺癌病例。的 这2400例，600例是小细胞肺癌的新病例 (SCLC)。这项建议旨在研究和开发潜力 抑制小细胞肺癌生长的药物 小细胞肺癌产生的某些多肽激素的形成 细胞。已知这些多肽激素通过以下方式影响小细胞肺癌 增加了其异常增长的潜力。假设 我们将测试的是小细胞肺癌产生代谢“副产物”多肽 荷尔蒙通过蛋白质分解代谢较大的“母体”蛋白质， 这些多肽会导致小细胞肺癌的生长。如果我们能控制住 通过抑制这些多肽激素的产生 负责它们形成的酶，那么我们也许能够 控制小细胞肺癌生长。我们的研究方法可以被视为 试图中断导致SCLC的一连串事件 通过改变必要催化剂的形成来实现生长 (多肽)引起这种疾病的许多症状。 我们的长期目标是开发一种药物(肽酶抑制剂) 能够作用于小细胞肺癌产生的多肽。以这种方式 我们将控制SCLC的增长，也将控制 多肽激素的形成具有严重的和 小细胞肺癌过度分泌所致的不良副作用 细胞。

Small cell lung cancer (i.e. small oat-cell carcinoma) accounts for approximately 25% of all identifiable human lung cancers. This malignant neoplasm has a rapid growth rate and shows a propensity to metastasize and grow rapidly. In Arizona alone, there are 2,400 new cases of lung cancer diagnosed each year. Of these 2,400 cases, 600 are new cases of small cell lung cancer (SCLC). This proposal is designed to study and develop potential inhibitors of small cell lung cancer growth by inhibiting the formation of certain peptide hormones produced by the SCLC cells. These peptide hormones are known to affect SCLC by increasing its potential for abnormal growth. The hypothesis that we will test is that SCLC produces metabolic "byproduct" peptide hormones by proteolytic metabolism of larger "parent" proteins, and that these peptides cause SCLC to grow. If we can control the production of these peptide hormones by inhibiting the enzymes responsible for their formation, then we may be able to control SCLC growth. Our research approach can be seen as attempting to disrupt a cascade of events responsible for SCLC growth by altering the formation of the necessary catalysts (peptides) responsible for many of the symptoms of the disease. Our long term objective is to develop a drug (peptidase inhibitor) capable of acting on peptides produced from SCLC. In this way we will be controlling the growth of SCLC, and also controlling the formation of peptide hormones which have serious and deleterious side effects due to their hypersecretion from SCLC cells.